Amino acids are often employed as raw materials in the preparation, by a sequence of reactions, of compounds having various uses. In many of these sequences it is necessary to reversibly block a primary amino group of the amino acid or its salts in order that the blocked compound may undergo further reactions which would otherwise irrevocably destroy the amino group, and yet permit later regeneration of the primary amino group.
Benzyloxycarbonyl is eminently suited as the blocking group for these purposes. See for example, U.S. Pat. No. 4,293,706, Floyd et al, "Monobactams . . . ", Journal of Organic Chemistry, Vol. 47, No. 1, pages 176-178 (1982), Cimarusti et al, "Monobactams . . . ", Journal of Organic Chemistry, Vol. 47, pages 179-180 , and Wertheim, Textbook of Organic Chemistry, 3d edition, pages 808-809 (1951), the entire disclosures of which are incorporated herein by reference. The benzyloxycarbonyl group may be introduced by reacting alkali metal salt of the amino acid with a benzylhaloformate, such as benzylchloroformate of benzylbromoformate, in a polyphase reaction mixture.
When the amino acid contains, in addition to a primary amino group and at least one carboxylate anion, at least one fuctional group selected from the class consisting of hydroxyl, additional primary amino, secondary amino, primary imido, and primary amido, product yields are reduced due to the undesired side reaction of the benzylhaloformate with the additional functionality. A hydroxyl group, for instance, can and often does react with the benzylhaloformate to form an undesired carbonate. It is important to observe that loss of product by this mechanism pertains only to those amino acids containing the additional functionality; it does not pertain to those amino acids which do not contain the additional functionality.
Crown ethers and silacrown ethers are known phase-transfer reagents which have been employed for various reactions. See, for example U.S. Pat. Nos. 3,562,295; 3,686,225; and 3,687,978; and Gokel and Durst, "Principles and Synthetic Applications in Crown Ether Chemistry", Synthesis, March 1976, pages 168-184; Starks and Liotta, Phase Transfer Catalysts-Principles and Techniques, Academic Press, New York, pages 77-90 (1978); Arkles et al, "Silacrowns: Phase-Transfer Catalysts", Organometallics, Vol. 2, No. 3, pages 454-457 (1983); and Product Data Sheet, Silanes for Phase Transfer Catalysis, Petrarch Systems, Inc., Bristol, Pa., the entire disclosures of which are incorporated herein by reference. Neither the crown ethers nor the silacrown ethers have, however, been employed as phase-transfer reagents in blocking a primary amino group of an amino acid having the additional functionality discussed above.